sinoporphyrin-sodium and Glioblastoma

Sonodynamic therapy (SDT) is a promising modality for cancer treatment. Sinoporphyrin sodium (DVDMS), purified from Photofrin II, shows great potential in SDT evidenced by growing studies. The purpose of the current study was to investigate the antitumor effect of SDT combined with DVDMS on human glioblastoma (U87 MG) cell line in vitro. The cellular uptake of DVDMS was investigated by confocal microscopy and IVIS spectrum imaging system. In addition, DVDMS toxicity and anti-tumor effect of SDT were assessed by flow cytometry. The generation of intracellular reactive oxygen species (ROS) was determined using DCFH-DA staining. Simultaneously, fluorescence microscopy was performed to access the destabilization of mitochondrial membrane potential (MMP). The results showed that DVDMS could easily enter the cells and accumulated in the cytoplasm, especially the mitochondria. And the intracellular DVDMS increased with incubation time or concentrations. The results also showed remarkable cytotoxicity of DVDMS-mediated SDT (center frequency: 0.970 MHz; peak-rarefactional pressure: 0.52-MPa; acoustic power: 0.32 W; pulse repetition frequency: 1 Hz; duty cycle: 1-30%; duration: 3 min) on U87 MG cells, while DVDMS alone was non-toxic to the cells. In comparison with the control group, the SDT-treated group showed significant generation of intracellular ROS and loss of MMP at 1 h post-treatment. These results indicated that DVDMS-mediated SDT could induce great cytotoxicity in U87 MG cells via the production of ROS and showed potentials in the treatment for glioblastoma.

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Equipment Design; Glioblastoma; Humans; In Vitro Techniques; Membrane Potential, Mitochondrial; Necrosis; Porphyrins; Reactive Oxygen Species; Ultrasonic Therapy

Sonodynamic therapy (SDT) is a promising noninvasive method for cancer treatment. The anti-tumor effect of sinoporphyrin sodium (DVDMS)-mediated SDT on nude mice bearing intracranial U87 MG-Red-FLuc human glioblastoma was investigated. Focused ultrasound (FUS) with microbubbles (MBs) was utilized to open the blood-brain barrier for enhancing the delivery of the sonosensitizer DVDMS to the brain tumor first, and then the SDT treatment was performed. The in vitro study showed obvious cytotoxicity of DVDMS-mediated SDT (center frequency: 0.996 MHz, acoustic power: 1.7 W, pulse repletion frequency: 1 Hz, duty cycle: 30%, duration: 1 min) on U87 MG-Red-FLuc cells. The results indicated that more DVDMS accumulation in the tumor sites was induced by FUS with MBs by 3.43 folds of unsonicated ones. Longitudinal bioluminescence imaging illustrated that the intracranial glioblastoma progression in nude mice treated with SDT was retarded compared to the untreated group. The median survival time was prolonged to 30.25 days after SDT treatment by 27.37%. The anti-proliferation effect and cell apoptosis induction was further confirmed by immunohistochemical examinations. These results of the study suggested that SDT using the sonosensitizer DVDMS delivered by FUS with MBs may provide a new promising therapeutic strategy against glioblastoma.

Topics: Animals; Blood-Brain Barrier; Brain Neoplasms; Cell Line, Tumor; Contrast Media; Diagnostic Imaging; Glioblastoma; Heterografts; Humans; Luminescent Measurements; Mice, Nude; Microbubbles; Neoplasm Transplantation; Porphyrins; Ultrasonic Therapy